The finding by USC researchers (University of Southern
California Health News, 12/02/2016 http://news.usc.edu/111841/male-vs-female-stress-responses-may-explain-sex-differences-in-diseases/)
may explain how Alzheimer’s and Parkinson’s affect men and women.
The differences in how male and female fruit flies resist
and adapt to oxidative stress may shed new light on how age–related diseases
such as Alzheimer’s and Parkinson’s affect men and women differently.
Through a series of tests, USC researchers found that female
fruit flies were better able to respond to stress caused by a common oxidant,
hydrogen peroxide (produced naturally in the body for cell signaling and to
combat infection), than males. However, males were better able to adapt to
another oxidant, paraquat, a common herbicide.
Both oxidants have been implicated in human diseases.
Elevated levels of hydrogen peroxide are found in patients suffering from a
stroke, a heart attack or Alzheimer’s disease. Paraquat is one of the
environmental toxins that can damage the neurons involved in Parkinson’s
disease, which attacks the nervous system.
The male and female responses to the stress seem to differ
in part because of a protein, Lon protease, that localizes to mitochondria, the
researchers found.
The researchers’ findings, published in the journal Current
Biology on Dec. 1, indicate the need for further investigation into sex–based
differences in the biological responses of men and women, particularly as
scientists consider new ways to treat age–related diseases, Tower said.
Laura C.D. Pomatto, Caroline Carney, Brenda Shen, Sarah
Wong, Kelly Halaszynski, Matthew P. Salomon3, Kelvin J.A. Davies, John Tower. The Mitochondrial Lon Protease Is Required
for Age-Specific and Sex-Specific Adaptation to Oxidative Stress. Current
Biology. In press.
Highlights
•Female-specific H2O2 and male-specific paraquat stress
adaptation require Lon
•Sex-specific expression of Lon protein isoforms
•Sex-specific Lon expression and stress adaption are
regulated by transformer
•Sex-specific expression of Lon isoforms is observed in
mammalian tissues
Summary
Multiple human diseases involving chronic oxidative stress
show a significant sex bias, including neurodegenerative diseases, cancer,
immune dysfunction, diabetes, and cardiovascular disease. However, a possible
molecular mechanism for the sex bias in physiological adaptation to oxidative
stress remains unclear. Here, we report that Drosophila melanogaster females
but not males adapt to hydrogen peroxide stress, whereas males but not females
adapt to paraquat (superoxide) stress. Stress adaptation in each sex requires
the conserved mitochondrial Lon protease and is associated with sex-specific
expression of Lon protein isoforms and proteolytic activity. Adaptation to
oxidative stress is lost with age in both sexes. Transgenic expression of
transformer gene during development transforms chromosomal males into
pseudo-females and confers the female-specific pattern of Lon isoform
expression, Lon proteolytic activity induction, and H2O2 stress adaptation;
these effects were also observed using adult-specific transformation.
Conversely, knockdown of transformer in chromosomal females eliminates the
female-specific Lon isoform expression, Lon proteolytic activity induction, and
H2O2 stress adaptation and produces the male-specific paraquat (superoxide)
stress adaptation. Sex-specific expression of alternative Lon isoforms was also
observed in mouse tissues. The results develop Drosophila melanogaster as a
model for sex-specific stress adaptation regulated by the Lon protease, with potential
implications for understanding sexual dimorphism in human disease.
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